The molecular and cellular bases for certain aspects of drug addiction have been well established recently. Researchers understand a great deal about how drugs operate at their primary targets, as well as how they bring about long-term cellular, molecular, and behavioral alterations. Noticeably missing, however, are effective treatments for addicted individuals. The challenge is to understand why relapse is so prevalent. One possible explanation for the high rate of relapse is the conditioning effects of drugs. Drug-associated cues can evoke strong cravings in former drug users, and can be a powerful determinant of relapse to drug use. While this behavior is well characterized, very little is known about the cellular and molecular bases for drug- associated conditioned behavior. The proposed research will investigate the neurochemical, gene regulatory, and signal transduction mechanisms involved in both the development and expression of a conditioned response induced by repeated morphine treatment, as well as how it relates to other conditioning paradigms. The guiding notion is that a better understanding of the basic cellular processes at work during drug-associated conditioning may lead to better treatments for addicted individuals.